Notopterol mitigates IL-1β-triggered pyroptosis by blocking NLRP3 inflammasome via the JAK2/NF-kB/hsa-miR-4282 route in osteoarthritis

Ko Ta Chen, Chi Tai Yeh, Vijesh Kumar Yadav, Narpati Wesa Pikatan, Iat Hang Fong, Wei Hwa Lee, Yen Shuo Chiu

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

Objective: Osteoarthritis (OA), the most prevalent form of arthritis, impacts approximately 10% of men and 18% of women aged above 60 years. Currently, a complete cure for OA remains elusive, making clinical management challenging. The traditional Chinese herb Notopterygium incisum, integral to the Juanbi pill for rheumatism, shows promise in safeguarding chondrocytes through its strong anti-inflammatory effects. Methods: To explore the protective effect of notopterol and miRNA (has-miR-4248) against inflammation, we simulated an inflammatory environment in chondrocytes cell lines C20A4 and C28/12, focusing on inflammasome formation and pyroptosis. Results: Our finding indicates notopterol significantly reduced interleukin (IL)-18 and tumor necrosis factor (TNF)-alpha levels in inflamed cells, curtailed reactive oxygen species (ROS) production post-inflammation, and inhibited the JAK2/STAT3 signaling pathway, thus offering chondrocytes protection from inflammation. Importantly, notopterol also hindered inflammasome assembly and pyroptosis by blocking the NF-κB/NLRP3 pathway through hsa-miR-4282 modulation. In vivo experiments showed that notopterol treatment markedly decreased Osteoarthritis Research Society International (OARSI) scores in OA mice and boosted hsa-miR-4282 expression compared to control groups. Conclusions: This study underscores notopterol's potential as a therapeutic agent in OA treatment, highlighting its capacity to shield cartilage from inflammation-induced damage, particularly by preventing pyroptosis.

Original languageEnglish
Article numbere28094
JournalHeliyon
Volume10
Issue number6
DOIs
Publication statusPublished - Mar 30 2024

Keywords

  • Interleukin 1 beta
  • JAK2/NF-κB/hsa-miR-4282 pathway
  • NLRP3 inflammasome
  • Notopterol
  • Osteoarthritis
  • Pyroptosis

ASJC Scopus subject areas

  • General

Fingerprint

Dive into the research topics of 'Notopterol mitigates IL-1β-triggered pyroptosis by blocking NLRP3 inflammasome via the JAK2/NF-kB/hsa-miR-4282 route in osteoarthritis'. Together they form a unique fingerprint.

Cite this